This is an application for the renewal of NIMH Independent Scientist Award K02 MH01046, "Genetic Regulation of Telecephalon Development," for John L. R. Rubenstein, M.D., Ph.D. There is abundant evidence to suggest that neuropsychiatric disorders such as schizophrenia and autism are caused in many cases by genetic abnormalities that affect development and function of forebrain neural systems involved in cognition and emotion. The largest structures of the forebrain are the cerebral cortex and the striatum; both have been implicated as having a role in neuropsychiatric disorders. The goal of my research is to understand how genes regulate development of the striatum. To this end, my laboratory has identified the Dlx genes, which encode a family of homeodomain transcription factors that are candidates for having a central role in striatal development. The aims of the experiments proposed in this grant application are focused on (1) elucidating the sequence of these genes and their encoded proteins, (2) determining the intracellular location of the DLX proteins, (3) determining the temporal and spatial patterns of expression of the Dlx RNAs and proteins in the prenatal and postnatal forebrain, (4) determining whether the DLX proteins are transcriptional regulators, (5) studying the effect of mutations of these genes on brain development, (6) identifying genes that are regulated by the Dlx genes, and (7) beginning to determine, using ectopic expression experiments, where the Dlx genes are in the genetic hierarchy that regulates development of the forebrain.